[gmx-users] Re: gmx-users Digest, Vol 79, Issue 167
Thomas Piggot
t.piggot at soton.ac.uk
Fri Nov 26 09:53:33 CET 2010
OK that makes things clearer. As I mentioned I would check that it is
not an issue with using CHARMM from 4.0.5 as if I remember correctly the
CHARMM forcefield was not fully supported until version 4.5 (and I think
was removed from the GROMACS 4.0.7 release so people didn't use it). As
I also mentioned someone else will know much more about this than me,
for example what changed between the 4.0.5 version of the forcefield
implementation and the 4.5 implementation. It may have been very little,
but I do not know. As for you seeing the same with different GROMACS
versions then I think this does not matter as you are using the same
4.0.5 topology with the different versions and it could be this topology
which is causing the issues.
The test to run to check if it is the charge groups which are causing
this behavior is to run simulations (probably with repeats so you sure)
using GROMACS 4.5.1 with and without the -nochargegrp option of pdb2gmx
and everything else the same. As to why you are seeing this (if it is
indeed something you can confirm) is another question and I am unsure,
it seems fairly strange. Again I am sure someone else with more
knowledge can comment on this.
Cheers
Tom
On 26/11/10 08:35, sa wrote:
> Hi Tom.
>
> Hi,
>
> You show differences when using GROMACS 4.5.3 for one simulation with
> the pdb2gmx option -nochargegrp and one without this option (is this
> correct, or did you manually edit the topology to have the old charge
> groups?). This pdb2gmx option should have no effect in 4.5.3 as
> all the
> entries in the CHARMM27 .rtp are in individual charge groups.
>
>
> I will try to be more clear here:
>
> First step: The two top files were generated with different rtp files.
> In the first case i used a rtp file where the charge groups for each
> AA were distributed as in the CHARMM27 ff distribution. The top file
> were generated the gromacs (4.0.5) and the following command
>
> pdb2gmx_mpi -ignh -ff charmm27 -ter -f hMRP1_K-TM17_AcAm.pdb -o
> hMRP1_K-TM17.gro -p hMRP1_K-TM17.top -missing
>
> For the second top i used gromacs 4.5 with the argument -nochargegrp
> (with one charge group assigned for atom) with the command
>
> pdb2gmx_mpi -ignh -ff charmm27 -ter -f hMRP1_K-TM17_AcAm-H.pdb -o
> hMRP1_K-TM17.gro -p hMRP1_K-TM17.top -missing -nochargegrp
>
> Second Step: i used the latest version of gromacs 4.5.3 to generate
> the different tpr files and performed the simulations with the two
> types of top files. In case of the MD with the others versions of
> gromacs, the step two was done with the cooresponding version of gromacs.
>
>
> If you didn't edit the 4.5.3 topology then either you are doing
> something else different between these simulations or what you
> think is
> a difference between simulations with and without this pdb2gmx
> option is
> just a coincidence and that your peptide is sometimes stable over this
> short 24 ns simulation and sometimes it unfolds, irrespective of the
> charge group option.
>
> I have also performed a MD during 100 ns (with -chargegroup), and in
> this case the peptide remains stable along the simulation time. I
> don't understand why. Moreover i dont think it is a coincidence since
> i observe the same results whatever the gmx version and md parameters
> used
>
>
> If you did edit the topology then are you sure that it is correct? Did
> you use 4.5.3 to get the topology and edit it by hand or did you
> generate this 'charge group' topology by some other method, such as
> another version of GROMACS? If you used the topology from 4.0.x then
> maybe there are issues here as I know CHARMM27 was not fully supported
> until 4.5.
>
>
> I didn't edit the top file manually, i used only the pdb2gmx tool.
> However by reading your message, i have take a look more deeper in te
> the top file and i have found differences in some directives (for
> example in the pair directive where there are more terms). =-O To be
> sure that this difference has no impact in the MD, i going to do other MD.
>
> I will come back soon. Thanks you again
>
> SA
>>
>
>
> Cheers
>
> Tom
>
> On 25/11/10 22:42, sa wrote:
> > Dear All,
> >
> > In a previous message
> >
> (http://lists.gromacs.org/pipermail/gmx-users/2010-November/055839.html),
> > I described the results obtained with MD performed with the CHARMM27
> > ff and the chargegrp "yes" and "no" options of a peptide in TIP3P
> > water simulated gromacs. Since these results puzzled me a lot, i
> would
> > like to share with you others results obtained from the gromacs
> > community advices to explain these results.
> >
> > In few words, the context of these simulations. One of my
> labmate did,
> > 8 months ago (march/april), several simulations of a peptide (25 AA)
> > with the CHARMM27 ff (and CMAP). The peptide is a transmembrane
> > segment (TM) and belongs to a large membrane protein. This TM
> segment
> > has an initial helical conformation. The simulations were
> performed in
> > a cubic box filled with app. 14000 TIP3P water (Jorgensen's model)
> > with 2 Cl ions. To construct the topology file of the system,
> > -chargegrp "yes" with pdb2gmx and the MD were done with the gromacs
> > 4.0.5. For some reasons, he had to left the lab, and my boss
> asked me
> > to continue his work. When I checked their results, i was very
> > intrigued by these MD results because he found that the peptide keep
> > along all the simulation time (100 ns) its initial helical
> > conformation. This results are not in agreement with circular
> > dichroism experiments which are shown that the same peptide in water
> > has no helix segment and is completely unfold. I am aware that the
> > simulation time is short compared to experiment time scale, however
> > since i haven't seen any unfolding events in this simulation, so
> I was
> > not very confident about these results.
> >
> > To explain this inconsistency, I have suspected that the error came
> > probably of the use of the default -chargegrp with CHARMM ff in
> these
> > simulations since i have read several recent threads about the
> charge
> > groups problems in the CHARMM ff implementation in gromacs. To
> examine
> > this hypothesis I have done two simulations with last gromacs
> version
> > (4.5.3) and two top files containing charge groups and no charge
> > groups for the peptide residus. I used the *same* initial pdb file,
> > box size and simulations parameters. The two simulations were
> carried
> > out during 24 ns in the NPT ensemble with the md.mdp parameters
> > described below after energy minimisation, NVT and NPT equilibration
> > steps.
> >
> > constraints = all-bonds
> > integrator = md
> > nsteps = 12000000 ; 24000ps ou 24ns
> > dt = 0.002
> >
> > nstlist = 10
> > nstcalcenergy = 10
> > nstcomm = 10
> >
> > continuation = no ; Restarting after NPT
> > vdw-type = cut-off
> > rvdw = 1.0
> > rlist = 0.9
> > coulombtype = PME
> > rcoulomb = 0.9
> > fourierspacing = 0.12
> > fourier_nx = 0
> > fourier_ny = 0
> > fourier_nz = 0
> > pme_order = 4
> > ewald_rtol = 1e-05
> > optimize_fft = yes
> >
> > nstvout = 50000
> > nstxout = 50000
> > nstenergy = 20000
> > nstlog = 5000 ; update log file every 10 ps
> > nstxtcout = 1000 ; frequency to write coordinates
> to xtc
> > trajectory every 2 ps
> >
> > Tcoupl = nose-hoover
> > tc-grps = Protein Non-Protein
> > tau-t = 0.4 0.4
> > ref-t = 298 298
> > ; Pressure coupling is on
> > Pcoupl = Parrinello-Rahman
> > pcoupltype = isotropic
> > tau_p = 3.0
> > compressibility = 4.5e-5
> > ref_p = 1.0135
> > gen_vel = no
> >
> > I found that with charge groups, the peptide remains in its initial
> > helical conformation, whereas with no charge group, the peptide
> > unfolds quickly and has a random coil conformation. I have shown
> these
> > results to my boss but I was not able to explain why we observe
> these
> > differences between the two simulations. Indeed since i use PME
> in the
> > MD, chargegroup should not affect the dynamic results (correct
> ?) . He
> > asked to do others simulations with different versions of gromacs to
> > see if is not a bug with charge group implementation in gromacs. For
> > testing i have done four others MD wit the *same* initial pdb file,
> > box size and simulations parameters and with previous GMX version
> > 4.5.0 and pre 4.5.2 and with the two types of top files.
> >
> > In addition since i have done simulations with non optimal parameter
> > for the vdW et electrostatic, i have also tested the influence
> of the
> > vdW et electrostatic MD parameters on the MD by performing two
> > additional simulations with the parameters used in the Bjelkmar
> et al
> > . paper (J. Chem. Theory Comput. 2010, 6, 459–466) (labeled
> GMX4.5.3
> > CHARMM in the figures)
> >
> > ; Run parameters
> > integrator = md ; leap-frog integrator
> > nsteps = 12000000 ; 2 * 1000000 = 20000 ps
> > dt = 0.002 ; 2 fs
> > nstcomm = 10
> > nstcalcenergy = 10
> > ; Output control
> > nstxtcout = 1000 ; frequency to write coordinates
> to xtc
> > trajectory every 10 ps
> > nstxout = 50000
> > nstvout = 50000 ; save velocities every 0.2 ps
> > nstenergy = 25000 ; save energies every 0.2 ps
> > nstlog = 5000 ; update log file every 0.2 ps
> > energygrps = protein Non-Protein
> > ; Bond parameters
> > continuation = yes ; continuation after NVT
> > constraint_algorithm = lincs ; holonomic constraints
> > constraints = all-bonds ; all bonds (even heavy atom-H
> bonds)
> > constrained
> > lincs_iter = 1 ; accuracy of LINCS
> > lincs_order = 4 ; also related to accuracy
> > ; Neighborsearching
> > ns_type = grid ; search neighboring grid cels
> > nstlist = 10 ; 20 fs
> > rlist = 1.2
> > ;
> > coulombtype = PME
> > rcoulomb-switch = 0
> > rcoulomb = 1.2
> > vdw-type = Switch
> > ; cut-off lengths
> > rvdw-switch = 1.0
> > rvdw = 1.2
> > DispCorr = EnerPres
> > table-extension = 5
> > fourierspacing = 0.14
> > fourier_nx = 0
> > fourier_ny = 0
> > fourier_nz = 0
> > pme_order = 4
> > ewald_rtol = 1e-05
> > ewald_geometry = 3d
> > epsilon_surface = 0
> > optimize_fft = no
> > ; Temperature coupling is on
> > tcoupl = nose-hoover ;
> > tc-grps = protein Non-Protein ; one coupling groups - more
> > accurate
> > tau_t = 0.4 0.4 ; time constant, in ps
> > ref_t = 297 297 ; reference temperature, one for
> each
> > group, in K
> > ; Pressure coupling is off
> > pcoupl = Parrinello-Rahman ; pressure
> coupling in NPT
> > pcoupltype = isotropic
> > tau_p = 3.0
> > compressibility = 4.5e-5
> > ref_p = 1.0135
> >
> > ; Periodic boundary conditions
> > pbc = xyz ; 3-D PBC
> > gen_vel = no
> >
> > The results are presented in the three figures accessibles with the
> > three links below
> >
> > http://img4.hostingpics.net/pics/586637ResultatsVSGMX1jpg.jpg ->
> > Conformation
> > http://img4.hostingpics.net/pics/392578ResultatsVSGMX2jpg.jpg ->
> > RMSD vs. time
> > http://img4.hostingpics.net/pics/271597ResultatsVSGMX3jpg.jpg ->
> > Secondary structure vs. time
> >
> > As you can see in all runs with no charge groups option, the peptide
> > quickly unfolds and have a random coil conformation during the end
> > of the simulation times, whereas with charge group option, the
> peptide
> > remains in its initial (helix) conformation whatever the gromacs
> > version used.
> >
> > To finish I saw that in all the simulation seems to be well
> conserved
> >
> > CHARGE GROUP 4.5.3 (along the 24 ns of the run)
> >
> > Energy Average Err.Est. RMSD Tot-Drift
> >
> -------------------------------------------------------------------------------
> > Potential -561452 5.6 774.891 -1.37923
> > (kJ/mol)
> > Total Energy -455901 5.6 959.234 -1.42286
> > (kJ/mol)
> >
> > NO_CHARGE GROUP 4.5.3 (along the 24 ns of the run)
> >
> > Energy Average Err.Est. RMSD Tot-Drift
> >
> -------------------------------------------------------------------------------
> > Potential -563934 18 774.632 -113.02
> > (kJ/mol)
> > Total Energy -458347 18 960.371 -112.951
> > (kJ/mol)
> >
> > CHARGE GROUP pre4.5.2 (along the 24 ns of the run)
> >
> > Energy Average Err.Est. RMSD Tot-Drift
> >
> -------------------------------------------------------------------------------
> > Potential -562415 5.1 777.12 -33.8615
> > (kJ/mol)
> > Total Energy -456864 5.1 964.365 -33.7504
> > (kJ/mol)
> >
> > NO_CHARGE_GROUP_PRE_4.5.2
> >
> > Energy Average Err.Est. RMSD Tot-Drift
> >
> -------------------------------------------------------------------------------
> > Potential -564899 4.6 778.002 -3.00182
> > (kJ/mol)
> > Total Energy -459312 4.6 963.702 -2.58102
> > (kJ/mol)
> >
> > NO_CHARGE_GROUP_PRE_4.5.0
> >
> > Energy Average Err.Est. RMSD Tot-Drift
> >
> -------------------------------------------------------------------------------
> > Potential -563933 30 777.279 -202.641
> > (kJ/mol)
> > Total Energy -458346 29 960.748 -202.578
> > (kJ/mol)
> >
> > CHARGE_GROUP_PRE_4.5.0
> >
> > Energy Average Err.Est. RMSD Tot-Drift
> >
> -------------------------------------------------------------------------------
> > Potential -561442 8 773.826 -49.7596
> > (kJ/mol)
> > Total Energy -455891 8 958.546 -49.7573
> > (kJ/mol)
> >
> > USE_CHARGE_GROUP_AND_GMX_4.5.3 AND CHARMM parameters settings
> >
> > Energy Average Err.Est. RMSD Tot-Drift
> >
> -------------------------------------------------------------------------------
> > Potential -566048 5.4 765.184 -31.6659
> > (kJ/mol)
> > Total Energy -460851 5.4 950.934 -31.7008
> > (kJ/mol)
> >
> > USE_NO_CHARGE_GROUP_AND_GMX_4.5.3 AND CHARMM parameters settings
> >
> > Energy Average Err.Est. RMSD Tot-Drift
> >
> -------------------------------------------------------------------------------
> > Potential -568520 24 770.264 -165.498
> > (kJ/mol)
> > Total Energy -463287 24 955.755 -165.768
> > (kJ/mol)
> >
> > I am particularly eager to obtain from you some comments and advices
> > about these findings. Thanks you so much for your help.
> >
> > SA
>
> --
> Dr Thomas Piggot
> University of Southampton, UK.
>
>
>
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>
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> End of gmx-users Digest, Vol 79, Issue 167
> ******************************************
>
>
--
Dr Thomas Piggot
University of Southampton, UK.
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